Methods 21 patients with juvenile or adult MLD (12 HCT-treated) were compared with 16 controls in the same age range. Clinical outcome was determined as good, moderate or poor. Metabolites were quantified in white matter, and significance of metabolite concentrations at baseline for outcome prediction was assessed using logistic regression analysis. Evolution of metabolic changes was assessed for patients with follow-up examinations.

Results In this retrospective study, 16 patients with baseline scans were included, 5 with good, 3 with moderate and 8 with poor outcome, and 16 controls. We observed significant group differences for all metabolite concentrations in white matter (p<0.001). Compared with controls, patients had decreased N-acetylaspartate and glutamate, and increased myo-inositol and lactate, most pronounced in patients with poor outcome (post hoc, all p<0.05). Logistic regression showed complete separation of data. Creatine could distinguish poor from moderate and good outcome, the sum of glutamate and glutamine could distinguish good from moderate and poor outcome, and N-acetylaspartate could distinguish all outcome groups. For 13 patients (8 with baseline scans), one or more follow-up examinations were evaluated, revealing stabilisation or even partial normalisation of metabolites in patients with moderate and good outcome, clearly visible in the ratio of choline/N-acetylaspartate.

Conclusion In MLD, quantitative spectroscopic imaging at baseline is predictive for outcome and aids in determining eligibility for HCT.

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Footnotes

NIW and PJWP contributed equally.

Contributors PJWP and NIW had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors substantially contributed to conception or design of the work, or the acquisition, analysis or interpretation of data. DFvR, PJWP and NIW wrote the manuscript. All authors critically revised the manuscript for intellectual content. All authors did a final review and approved the manuscript. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding This study was financed by Metakids, a charity sponsoring research on metabolic disorders (project 2015-059).

Competing interests None declared.

Patient consent Parental/guardian consent obtained.

Ethics approval The Institutional Review Board of the VU University Medical Center approved the study.

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